1uyj

Background
Epsilon toxin is produced by Clostridium perfringens of types B and D (Hunter, SE et al., 1992; Goswami, PP et al., 1996). It is secreted as an inactive prototoxin of 331 amino acids and of molecular weight 33 kDa (Hunter, SE et al., 1992).

Prototoxin activation can be done by proteases synthetized by the bacterium itself such as alpha-chymotrypsin and the lambda protease, or by several proteolytic enzymes of the digestive tract, such as trypsin. The lambda protease lambda acts on the N-terminal side by releasing an 11 amino acid peptide, and a stretch of 29 amino acids on the C-terminal side, whereas trypsin and alpha-chymotrypsin release a 13 amino acid-long stretch from the N-terminal end and a 29 amino acid stretch from the C-terminal end (Popoff, MR 2004). This proteolytic digestion gives the active form of the epsilon toxin, which is lethal, of molecular weight 29 KDa. This activation is concomitatnt with a slight modification of conformation and of the isoelectric point (pI) of the toxin. The prototoxin and the epsilon toxin are antigenetically identical (Habeeb, AF, 1969, 1975; Habeeb, AF et al., 1973), which confirms that the lost peptide is not an antigenic determinant of the molecule. The three-dimensional structure of the prototoxin is essentially formed by beta sheets, while that of the toxin is slightly transformed into alpha helical structure but with predominancy of the beta conformation (Habeeb, AF et al. 1973). It was shown that the structure of epsilon toxin is similar to that of Aeromonas hydrophila aerolysin (Cole, AR et al, 2004).

The epsilon toxin is encoded by the etx gene, carried by a plasmid (larger than 100 Kb, Hunter, SE et al., 1992) transferable horizontally from one strain to another (Frey J, 2003; Songer JG, 1996; Walker RL et al., 2004). It is a transposon gene (Daube, G et al., 1996). The gene from both B and D types was sequenced (Havard HL et al., 1992; Hunter, SE et al., 1992). The comparison between both sequences of the genes etxB and etxD shows a difference of two nucleotides in the coding part, that caused the substitution of a single amino acid (Havard HL et al., 1992).

The epsilon toxin is the most virulent factor in type D Clostridium perfringens; it interacts with vascular endothelial cells, provoking an increase of the permeability of vessels by damaging directly the endothelium which causes a loss of fluid and the appearance of oedema in particular of the lung, heart, kidneys and brain (Lefevre PC et al., 2003; Walker RL et al., 2004). The epsilon toxin is a powerful toxin which is responsible of fatal ovine enterotoxemy, of pulpy kidney disease, and of lamb dysentery.

About this Structure
1UYJ is a 3 chains structure of sequences from Clostridium perfringens. Full crystallographic information is available from OCA.